PROJECT SUMMARY: Brown, Solange P., Johns Hopkins University The broad goal of this proposal is to understand the types of cortical information that are integrated within the claustrum, a poorly understood brain structure that forms extensive reciprocal connections with the cortex. Studies have correlated abnormalities in the size and the activity of the claustrum with neuropsychiatric symptoms in diseases like Alzheimer's disease and schizophrenia, but the function of the claustrum remains unclear. A number of theories have been proposed regarding the claustrum's role in sensory processing and cognition, but the paucity of information on its cellular and functional organization has made it difficult to validate any of these theories. The proposed study will elucidate the cellular and functional organization of the claustrum to test three major current hypotheses: 1) that the claustrum plays a role in multimodal sensory integration, 2) that the claustrum plays a role in the bilateral coordination of sensorimotor behaviors involved in the exploration of the environment, and 3) that the claustrum plays a role in top-down control of the cortical response to sensory input. To test these hypotheses, we will use an innovative combination of approaches including rabies-based trans-synaptic tracing approaches, unitary recordings of synaptic connections among retrogradely and genetically labeled neurons, optogenetic circuit-mapping techniques, and in vivo studies. By assessing these theories of claustral function, we will determine mechanisms by which the claustrum influences cortical activity in the healthy brain and provide important insights into its contributions to abnormalities in sensory processing and cognition in neurologic and psychiatric diseases.